Virology Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD 21702, USA.
Pathology Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD 21702, USA.
Viruses. 2022 Jul 8;14(7):1502. doi: 10.3390/v14071502.
The purpose of this study was to evaluate the effects of the route of administration on the immunogenicity and efficacy of a combined western, eastern, and Venezuelan equine encephalitis (WEVEE) virus-like replicon particle (VRP) vaccine in cynomolgus macaques. The vaccine consisted of equal amounts of WEEV, EEEV, and VEEV VRPs. Thirty-three animals were randomly assigned to five treatment or control groups. Animals were vaccinated with two doses of WEVEE VRPs or the control 28 days apart. Blood was collected 28 days following primary vaccination and 21 days following boost vaccination for analysis of the immune response to the WEVEE VRP vaccine. NHPs were challenged by aerosol 28 or 29 days following second vaccination with WEEV CBA87. Vaccination with two doses of WEVEE VRP was immunogenic and resulted in neutralizing antibody responses specific for VEEV, EEEV and WEEV. None of the vaccinated animals met euthanasia criteria following aerosol exposure to WEEV CBA87. However, one NHP control (total of 11 controls) met euthanasia criteria after infection with WEEV CBA87. Statistically significant differences in median fever hours were noted in control NHPs compared to vaccinated NHPs, providing a quantitative measure of infection and efficacy of the vaccine against a WEEV challenge. Alterations in lymphocytes, monocytes, and neutrophils were observed. Lymphopenia was observed in control NHPs.
本研究旨在评估给药途径对一种包含西尼罗河病毒（WNV）、东部马脑炎病毒（EEEV）和委内瑞拉马脑炎病毒（VEEV）病毒样复制子颗粒（VRP）的中西东部马脑炎病毒（WEVEE）病毒样复制子颗粒（VRP）疫苗在食蟹猴中的免疫原性和疗效的影响。该疫苗由等量的 WEEV、EEEV 和 VEEV VRP 组成。33 只动物被随机分配到五个治疗或对照组。动物接受两次剂量的 WEVEE VRP 或对照疫苗，间隔 28 天。在初次接种后 28 天和加强接种后 21 天采集血液，用于分析对 WEVEE VRP 疫苗的免疫反应。在第二次接种后 28 或 29 天，用 WEEV CBA87 通过气溶胶对 NHPs 进行挑战。两次剂量的 WEVEE VRP 接种具有免疫原性，并导致针对 VEEV、EEEV 和 WEEV 的中和抗体反应。在气溶胶暴露于 WEEV CBA87 后，没有接种动物符合安乐死标准。然而，一只 NHP 对照（总共 11 只对照）在感染 WEEV CBA87 后符合安乐死标准。与接种疫苗的 NHPs 相比，对照 NHPs 中观察到中位数发热时间的统计学显著差异，这提供了感染和疫苗对 WEEV 挑战的疗效的定量衡量。观察到淋巴细胞、单核细胞和中性粒细胞的改变。在对照 NHPs 中观察到淋巴细胞减少。
